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Investigating inflammatory processes of plaque destabilization using proteomics

Lasse Lorentzen

SSAR 2022

Extracellular matrix remodeling in atherosclerosis

Extracellular matrix remodeling in atherosclerosis



  • Synthesis of new extracellular matrix (ECM) proteins
  • Degradation of “old” ECM proteins
  • Remodeling of the vascular ECM takes place under atherosclerotic conditions
  • Hypothesis: Remodeling of the vascular ECM is a key driver in plaque destabilization

Proteomics investigation of ECM remodelling

Proteomics workflow

Study design

  • 21 symptomatic plaques from the carotid artery
    • 7 Hard, 7 Mixed, 7 Soft plaques
  • Compared by proteomics

Differentially regulated proteins

Over-representation analysis

Over-representation analysis

N-terminomics investigation of protelytic ECM remodelling

ECM degradation by proteolytic enzymes

ECM degradation by proteolytic enzymes

ECM degradation by proteolytic enzymes

Proteomics workflow

ECM degradation by proteolytic enzymes

Differentially regulated free N-termini

Most regulated free N-termini are non-canonical

Degradation of Collagen type VI

Degradation of other Collagens

Degradation of Fibronectin

Degradation of other basement membrane proteins

Sequence motif analysis

Summary

  • Soft plaques are associated with lower level of ECM proteins
  • Soft plaques are associated with increased abundance of proteolytic enzymes
  • ECM proteins are subject to proteolytic degradation
  • ECM degradation is consistent with MMP activity

Thanks

  • Prof. Michael Davies
  • Prof. Henrik Sillesen, Prof. Jonas Eiberg, Karin Yeung
  • Christine Chuang
  • Protein Oxidation Group

Thank you for listening